Takeshi Yamamoto

Tohoku Pharmaceutical University, Sendai-shi, Miyagi, Japan

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Publications (11)18.13 Total impact

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    ABSTRACT: It has been reported that acute hepatitis B (AHB) patients with genotype A HBV (HBV/A) have been increasing since the 1990s in metropolitan areas in Japan. However, little is known about the trends of HBV genotypes in AHB patients in northeast Japan where genotype B HBV (HBV/B) prevails more than in other areas. In this study we aimed to clarify the changes in the HBV genotypes and clinical characteristics of AHB patients in this area. HBV genotypes were determined by direct sequencing (n = 125) or enzyme immunoassay (n = 9) using serum samples from AHB patients including fulminant hepatitis in 1987-2014. Among 134 patients, 26 (19%), 33 (25%), and 75 (56%) patients were infected with HBV of genotypes A, B, and C, respectively. HBV/A emerged from 2001 and the percentage was increased gradually up to 48% in 2010-2014, whereas HBV/B was reduced from 40% in 1987-1994 to 10% in 2010-2014. Phylogenetic analysis showed that 3 major subgenotype A2 strains had come into this area serially. The levels of HBV DNA and prothrombin time were higher in HBV/A patients than other genotypes. This study could not show significant difference in the HBsAg-positive period among genotypes nor the effect of nucleoside analogues to shorten the HBsAg-positive period. A higher level of initial HBV DNA was associated with late disappearance of HBsAg. In conclusion, the percentage of HBV/A in AHB patients has been increasing in northeast Japan since 2001, which is later than metropolitan areas, whereas that of HBV/B is decreasing. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Medical Virology 06/2015; DOI:10.1002/jmv.24309 · 2.35 Impact Factor
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    ABSTRACT: Two patients were referred to our hospital with cystic lesion (diameter 5 cm) of the pancreas and elevated serum CEA and CA19-9. We diagnosed them with malignant cystic neoplasms of the pancreas and performed distal pancreatectomy. Histologically, in both cases the cysts were lined with flat, transitional, squamoid cells without keratinization. Immunohistochemical staining confirmed two rare cases of squamoid cyst of the pancreatic ducts.
    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 05/2015; 112(5):896-904. DOI:10.11405/nisshoshi.112.896
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    ABSTRACT: The viral factors of hepatitis B virus (HBV), such as genotypes and mutations, were reported to affect the development of fulminant hepatitis B (FHB), but the mechanism is still unclear. To investigate HBV mutations associated with FHB, especially in the subgenotype B1/Bj HBV (HBV/B1), which are known to cause FHB frequently in Japan. A total of 96 serum samples from acute self-limited hepatitis B (AHB) patients and 13 samples from FHB patients were used for full-genome/partial sequencing. A total of 107 chronic infection patients with HBV were also examined for the distribution of mutants. In the analysis of full-genome sequences of HBV/B1 (FHB, n=11; non-FHB, n=35) including those from the databases, mutations at nt 1961 [T1961V (not T)] and nt 1962 [C1962D (not C)], which change S21 in the core protein, were found more frequently in FHB than in non-FHB (100% vs. 20%, 55% vs. 3%, respectively). When our FHB and AHB samples were compared, T1961V and C1962D were significantly more frequent in FHB than in AHB, both in the overall analysis (46% vs. 6%, 39% vs. 3%, respectively) and in HBV/B1 (100% vs. 29%, 100% vs. 14%, respectively). A newly developed PCR system detecting T1961V showed that HBV/B1 and low viral load were independent factors for the mutation among chronic infection patients. T1961V/C1962D mutations were found frequently in FHB, especially in HBV/B1. The resulting S21 substitution in the core protein may play important roles in the development of FHB.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 07/2012; 55(2):147-52. DOI:10.1016/j.jcv.2012.06.011 · 3.02 Impact Factor
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    ABSTRACT: BACKGROUND: The immunopathogenesis of dual chronic infection with hepatitis B virus and hepatitis C virus (HBV/HCV) remains unclear. The in vivo suppressive effects of each virus on the other have been reported. In this study we aimed to analyze the virological and immunological parameters of HBV/HCV coinfected patients during pegylated interferon/ribavirin (Peg-IFN/RBV) therapy. METHODS: One patient with high HBV-DNA and high HCV-RNA titers (HBV-high/HCV-high) and 5 patients with low HBV-DNA and high HCV-RNA titers (HBV-low/HCV-high) were enrolled. Twenty patients monoinfected with HBV and 10 patients monoinfected with HCV were enrolled as control subjects.. In vitro cultures of Huh 7 cells with HBV/HCV dual infection were used to analyze the direct interaction of HBV/HCV. RESULTS: Direct interaction of HBV clones and HCV could not be detected in the Huh-7 cells. In the HBV-high/HCV-high-patient, the HCV-RNA level gradually declined and HBV-DNA gradually increased during Peg-IFN/RBV therapy. Activated CD4- and CD8-positive T cells were increased at 1 month of Peg-IFN/RBV-therapy, but HBV-specific IFN-γ-secreting cells were not increased and HBV-specific interleukin (IL)-10 secreting cells were increased. The level of HBV- and HCV-specific IFN-γ-secreting cells in the HBV-high/HCV-high-patient was low in comparison to that in the HBV- or HCV-monoinfected patients. In the HBV-low/HCV-high-patient, HCV-RNA and HBV-DNA rapidly declined during Peg-IFN/RBV therapy. Activated CD4- and CD8-positive T cells were increased, and HBV- and HCV-specific IFN-γ-secreting cells were also increased during Peg-IFN/RBV-therapy. CONCLUSION: The immunological responses of the HBV-high/HCV-high patient were low in comparison to the responses in HBV and HCV monoinfected patients. Moreover, the response of immune cells in the HBV-high/HCV-high patient during Peg-IFN/RBV therapy was insufficient to suppress HBV and HCV.
    Journal of Gastroenterology 05/2012; 47(12). DOI:10.1007/s00535-012-0596-x · 4.52 Impact Factor
  • Takeshi Yamamoto · Kana Nishioka
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    ABSTRACT: Case 1 was a male aged 60 years old and Case 2 was a male in his 70s. They were asymptomatic, and visited our hospital with the complaint of abnormal liver function in the blood There was no involvement of viruses or drugs in either case. Liver biopsy showed only centrilobular zonal necrosis (CZN) and no chronic active hepatitis, which characterizes autoimmune hepatitis (AIH). From the serological facts of normal IgG levels and negative findings for various autoantibodies, we considered AIH to be unlikely, but successfully treated the condition with steroids. Because, especially in Case 1, liver function deteriorated upon discontinuation of steroid treatment, the disease was suspected to involve immune abnormalities. Even in patients with a serological dose not meeting AIH, one opinion was that CZN is an initial feature of AIH, but no conclusions were obtained. We consider that these 2 cases contribute to elucidation of this pathogenesis.
    Kanzo 01/2010; 51(12):730-735. DOI:10.2957/kanzo.51.730
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    ABSTRACT: A 82-year-old asymptomatic HBV carrier man was admitted with liver dysfunction in May 2007. With anti-HBe antibody and high viral load, he had fulminant hepatic failure without proximate cause. He was treated with entecavir and corticosteroids, but died about one month later. Autopsy specimen of liver revealed submassive hepatic necrosis with faint regeneration. HBV obtained was segregated into genotype Bj, and mutation was detected at nt1896 in a precore region.
    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 01/2009; 105(12):1781-6.
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    ABSTRACT: To evaluate the efficacy of pegylated interferon alpha-2b (peg-IFN alpha-2b) plus ribavirin (RBV) therapy in Japanese patients with chronic hepatitis C (CHC) genotype Ib and a high viral load. One hundred and twenty CHC patients (58.3% male) who received peg-IFN alpha-2b plus RBV therapy for 48 wk were enrolled. Sustained virological response (SVR) and clinical parameters were evaluated. One hundred (83.3%) of 120 patients completed 48 wk of treatment. 53 patients (44.3%) achieved SVR. Early virological response (EVR) and end of treatment response (ETR) rates were 50% and 73.3%, respectively. The clinical parameters (SVR vs non-SVR) associated with SVR, ALT (108.4 IU/L vs 74.5 IU/L, P = 0.063), EVR (76.4% vs 16.4%, P < 0.0001), adherence to peg-IFN (>or= 80% of planned dose) at week 12 (48.1% vs 13.6%, P = 0.00036), adherence to peg-IFN at week 48 (54.7% vs 16.2%, P < 0.0001) and adherence to RBV at week 48 (56.1% vs 32.1%, P = 0.0102) were determined using univariate analysis, and EVR and adherence to peg-IFN at week 48 were determined using multivariate analysis. In the older patient group (> 56 years), SVR in females was significantly lower than that in males (17% vs 50%, P = 0.0262). EVR and adherence to Peg-IFN were demonstrated to be the main factors associated with SVR. Peg-IFN alpha-2b plus RBV combination therapy demonstrated good tolerability in Japanese patients with CHC and resulted in a SVR rate of 44.3%. Treatment of elderly female patients is still challenging and maintenance of adherence to peg-IFN alpha-2b is important in improving the SVR rate.
    World Journal of Gastroenterology 12/2008; 14(47):7225-4230. · 2.37 Impact Factor
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    ABSTRACT: Many studies have reported the efficiency of transient elastography, a noninvasive, reproducible, and reliable method for predicting liver fibrosis, in patients with chronic hepatitis C (CHC) and B (CHB), but there are few reports about nonviral chronic liver disease (CLD) such as primary biliary cirrhosis (PBC), nonalcoholic steatohepatitis (NAFLD), and autoimmune hepatitis (AIH). We therefore compared the efficiency of transient elastography between CHC and nonviral CLD. We assessed the accuracy of liver stiffness measurement (LSM) using Fibroscan, and compared these values with those of hyaluronic acid, type 4 collagen, platelet count, prothrombin index, and AST/platelet ratio index (APRI) as indices for the diagnosis of liver fibrosis in 114 patients with a variety of chronic liver diseases: CHC (n = 51), CHB (n = 11), NAFLD (n = 17), PBC (n = 20), and AIH (n = 15). The histology was assessed according to the METAVIR score by two pathologists. The number of fibrosis stage (F0/1/2/3/4) with CHC was 9/15/12/6/10, and that with nonviral CLD was 10/21/11/4/6, respectively. The ability, assessed by area under receiver operating characteristic (AUROC) curve, to predict liver fibrosis F >or= 2 for LSM, HA, type 4 collagen, platelet count, prothrombin index, and APRI, was 0.92, 0.81, 0.87, 0.85, 0.85, and 0.92 in CHC patients, respectively; and 0.88, 0.72, 0.81, 0.67, 0.81, and 0.77 in nonviral CLD patients, respectively. In patients with nonviral CLD, LSM was most helpful in predicting significant fibrosis (F >or= 2). Transient elastography is a reliable method for predicting significant liver fibrosis, not only in CHC patients but also in nonviral CLD patients.
    Journal of Gastroenterology 09/2008; 43(9):720-8. DOI:10.1007/s00535-008-2225-2 · 4.52 Impact Factor
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    ABSTRACT: A 26-year-old woman was admitted to our hospital with jaundice. Under a diagnosis of biliary and duodenal stenosis due to so called "groove pancreatitis", prednisolone (30 mg/day, 2 weeks) was administered. But these stenosis did not improve after the treatment, and pancreaticoduodenectomy was performed. Histologically, poorly differentiated adenocarcinoma was found in the "groove" between the duodenum and the pancreatic head. We should be kept of "pancreatic groove carcinoma" in mind when making a diagnosis of "groove pancreatitis".
    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 08/2008; 105(7):1078-86.
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    ABSTRACT: Hepatitis B virus (HBV) infection, which causes liver cirrhosis and hepatocellular carcinoma, remains a major health problem in Asian countries. Recent development of vaccine for prevention is reported to be successful in reducing the size of chronically infected carriers, although the standard medical therapies have not been established up to now. In this report, we encountered a patient with decompensated HBV-related cirrhosis who exhibited the dramatic improvements after antiviral therapy. The patient was a 50-year-old woman. Previous conventional medical treatments were not effective for this patient, thus this patient had been referred to our hospital. However, the administration of lamivudine, a reverse transcriptase inhibitor, for 23 months dramatically improved her liver severity. During this period, no drug resistant mutant HBV emerged, and the serum HBV-DNA level was continuously suppressed. These virological responses were also maintained even after the antiviral therapy was discontinued. Moreover, both hepatitis B surface antigen and e antigen were observed to have disappeared in this patient. The administration of lamivudine to patients with HBV-related cirrhosis, like our present case, should be considered as an initial medical therapeutic option, especially in countries where liver transplantation is not reliably available.
    The Tohoku Journal of Experimental Medicine 10/2006; 210(1):29-36. DOI:10.1620/tjem.210.29 · 1.35 Impact Factor
  • Gastroenterologia Japonica 28(6).

Publication Stats

52 Citations
18.13 Total Impact Points


  • 2015
    • Tohoku Pharmaceutical University
      Sendai-shi, Miyagi, Japan
  • 2012
    • Tokyo Kosei Nenkin Hospital
      Edo, Tōkyō, Japan
  • 2008
    • Tohoku University
      • Department of Gastroenterology
      Sendai-shi, Miyagi-ken, Japan
    • Hoshigaoka Koseinenkin Hospital
      Hirakata, Ōsaka, Japan